2h Neuroscience with Pharmacology
Functions and Mechanisms of Reflexes
Neuroscience is studied at many different levels: from brain, to system,
network, neurone, synapse, and molecule...
Top
Up
Down
René Descartes
“Cogito, ergo sum”
(“I think therefore I am”)
Bottom
Santiago Ramon y Cajal (ca 1900) : the Neurone Doctrine
1. Neurones and synapses
2. The monosynaptic stretch reflex
3. Polysynaptic reflexes
4. Synaptic integration (EPSP’s/IPSP’s)
5. The challenge of reconnecting
damaged circuitry: spinal injury
Neurones in the “Brainbow” transgenic mouse
brain are multi-coloured
ca. 1900: Sherrington proposes the concept of the “synapse”
“So far as our present knowledge goes we are led to think that
the tip of the [axon’s] arborescence is not continuous with but
merely in contact with the substance of the dendrite or cell
body on which it impinges. Such a special connection of one
nerve cell with another might be called a
synapse.”
C.S. Sherrington;
in Foster,M. A Textbook of Physiology. 7th edn. 1897
συν − together
απτειν − to clasp
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The brain is mostly synapses (1000 times more synapses than neurones)
Cerebral cortex (rat)
1 µm
Integrated Circuit
Number of Transistors in Intel Pentium
Dual Core microprocessor :
1.67x 108
Number of Neurones in 1 Human Brain : ~ 1010- 1012
Number of Synaptic Connections in 1 Human Brain : ~ 1015
Human Population of Planet Earth: 6.98 x 109
Prof Ribchester
Neuroscience is studied at many different levels: from brain, to system,
network, neurone, synapse, and molecule...
Top
1. Neurones and synapses
2. The monosynaptic stretch reflex
Middle
3. Polysynaptic reflexes
4. Synaptic integration (EPSP’s/IPSP’s)
5. The challenge of reconnecting
damaged circuitry: spinal injury
Bottom
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Dorsal (Posterior)
Afferent
Efferent
Ventral (Anterior)
Let’s build a brain, connecting input and output neurones ….
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A “monosynaptic” reflex
Initiation
Conduction
Transmission
End effect
Muscle spindles monitor muscle stretch/length
Yabushita et al (2006) J DENTAL RES, Vol. 85, No. 9, 849-853 (2006)
http://upload.wikimedia.org/wikipedia/commons/6/67/Spindle.GIF
http://content.answers.com/main/content/img/oxford/Oxford_Food_Fitness/0198631472.muscle.1.jpg
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Glutamate and ACh are neurotransmitters in the monosynaptic stretch reflex
glutamate
Sensory receptors in skeletal muscle.
Skeletal (Extrafusal) muscle
Extrafusal (skeletal) muscle fiber
Muscle spindle
Intrafusal muscle fibers
Nuclear bag fiber
Nuclear chain fiber
Equatorial region
Polar regions
Muscle spindle primary afferent (Ia)
Ia facilitatory reflex connections
Muscle spindle secondary afferent (II)
Golgi tendon organ (GTO)
GTO primary afferent (Ib)
Ib inhibitory reflex connections
Inhibitory interneuron
Dorsal (Posterior) spinocerebellar tract
Ventral (Anterior) spinocerebellar tract
Alpha lower motor neuron
Dynamic gamma lower motor neuron
Static gamma lower motor neuron
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+
Acetylcholine
EPSP
http://www.csus.edu/indiv/m/mckeoughd/AanatomyRev/mm_recept/mmReceptors.htm
1. Neurones and synapses
2. The monosynaptic stretch reflex
Charles Sherrington
3. Polysynaptic reflexes
4. Synaptic integration (EPSP’s/IPSP’s)
5. The challenge of reconnecting
damaged circuitry: spinal injury
From : Sherrington,C.S.(1906/47). The integrative action of the nervous
system. Cambridge University Press
Reciprocal
Inhibition:
Flexion
withdrawal
reflex
Crossed
Extension
reflex
A disynaptic
reflex
http://www.colorado.edu/intphys/Class/IPHY3730/image/figure5-24.jpg
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….increasing the complexity:
Synaptic potentials underlie reflex
excitation and inhibition
GABA
+
EPSP
+
+/-
-
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glutamate
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+/-
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Acetylcholine
Glycine
Acetylcholine
John Eccles
IPSP
Input
Integration
Output
Dendrites
1. Neurones and synapses
2. The monosynaptic stretch reflex
Soma
3. Polysynaptic reflexes
Orthodromic conduction
4. Synaptic integration (EPSP’s/IPSP’s)
5. The challenge of reconnecting
damaged circuitry: spinal injury
Axon Hillock
Initial Segment
Myelinated axon
Spatial
summation
Temporal summation
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Synaptic facilitation
http://snnap.uth.tmc.edu/images/examples/PSM_fcln.gif
Synaptic depression
1. Neurones and synapses
2. The monosynaptic stretch reflex
3. Polysynaptic reflexes
4. Synaptic integration (EPSP’s/IPSP’s)
5. The challenge of reconnecting
damaged circuitry: spinal injury
http://snnap.uth.tmc.edu/images/examples/PSM_deprsn.gif
Axons do not regenerate after spinal cord
transection
Stem cell therapies may
facilitate spinal cord
regeneration
The “Final Common Path”….
Raisman G. Olfactory ensheathing cells and repair of brain and
spinal cord injuries. Cloning Stem Cells. 2004;6(4):364-8.
Li, Field & Raisman (2005) Science 26
September 1997:Vol. 277. no. 5334,
pp. 2000 - 2002
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Specialised physiotherapies may enhance (“train”)
the function of spinal reflex circuits and synapses
….increasing
the complexity:
….add
plasticity
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Input
Adaptive
Integration
Output
Summary
1. Neuroscience is studied at many levels: from clinical to basic; from
systems to cells to molecules
2. Complex neural functions arise from the ways neurones are connected at
synapses, in specific neural circuits
3. The “monosynaptic” stretch reflex (knee-jerk reflex) is an example of the
simplest neural circuit; it involves only two neurones: a primary afferent
sensory neurone and an efferent motor neurone
4. Information is encoded in the pattern and frequency of action potentials
and in the size and shape of synaptic potentials.
5. EPSPs and IPSPs mediate excitatory and inhibitory synaptic
transmission respectively, using distinct neurotransmitters (e.g.
glutamate, excitatory; GABA, inhibitory) and specific receptors.
6. Multi-synaptic excitatory and inhibitory spinal reflexes are integrated to
generate complex motor patterns, refined by learning (“plasticity”)
7. Engineering recovery from spinal injury requires reconnection of injured
descending motor pathways to intact spinal reflex circuits
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